Chronic kidney disease (CKD) affects more than 25 million American adults. Kidney failure leads to the retention of metabolic waste products that functionally disrupt multiple tissues, including skeletal muscle. CKD patients have markedly reduced skeletal muscle mass and strength, which adversely impacts ambulation, functional independence, and quality of life. Previous evidence and our preliminary data suggest that mitochondrial dysfunction may be a central mechanism of skeletal muscle impairment in CKD. However, previous studies lack comprehensive assessments of key functional mitochondrial characteristics, may be confounded by other conditions inherent to CKD, and lack correlation with real-world physical performance measures. The goal of this application is to directly measure functional muscle mitochondrial properties in a broad cohort of CKD patients. We will utilize non-invasive magnetic resonance imaging and optimal spectroscopy tools to quantify muscle mitochondrial characteristics and will evaluate their associations with clinically relevant physical performance measures. We will then conduct a pilot trial to determine whether an aerobic and resistance training program plus coenzyme Q10 can modify mitochondrial functional properties in CKD. 1